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A genetic risk score comprising known venous thromboembolism loci is associated with chronic venous disease in a multi-ethnic cohort.

ABSTRACT: Chronic venous disease is common and shares some risk factors with venous thromboembolism (VTE). Several genetic loci have been discovered and well-replicated for VTE in European descent populations. We examined associations of a genetic risk score (GRS), comprising known VTE loci, with chronic venous disease.The San Diego Population Study (SDPS) is a multi-ethnic cohort that evaluated 2404 men and women aged 29-91 from 1994 to 1998 for chronic venous disease. The current study includes 1447 participants genotyped for 33 variants in 22 established VTE risk loci. Using these variants, unweighted and weighted GRS were constructed. Logistic regression was used to examine associations with venous disease.In non-Hispanic whites, African-Americans, Hispanics, and Asians, each standard deviation increment higher of the unweighted 33-SNP GRS was associated with a 1.45-fold (95% CI (1.26, 1.67)), 1.74-fold (1.18, 2.55), a 1.80-fold (1.30, 2.51), and 1.88-fold (1.30, 2.73) greater odds, respectively, for moderate plus severe disease. The difference in c-statistics was significant between a known venous risk factor model and a model adding the 33-SNP GRS for whites (p=0.008), African-Americans (0.03), and Hispanics (p=0.04), with marginal significance in Asians (p=0.06).GRS comprising variants primarily from VTE findings in European descent populations were associated with chronic venous disease across all race/ethnic groups, and contributed significantly to prediction, indicating some level of generalizability to other race/ethnic groups. Future work should focus on more in depth examination of racial/ethnic group genetic architecture in relation to chronic venous disease.

SUBMITTER: Wassel CL

PROVIDER: S-EPMC4718662 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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A genetic risk score comprising known venous thromboembolism loci is associated with chronic venous disease in a multi-ethnic cohort.

Wassel Christina L CL Rasmussen-Torvik Laura J LJ Callas Peter W PW Denenberg Julie O JO Durda J Peter JP Reiner Alexander P AP Smith Nicholas L NL Allison Matthew A MA Rosendaal Frits R FR Criqui Michael H MH Cushman Mary M

Thrombosis research 20150926 5

<h4>Background</h4>Chronic venous disease is common and shares some risk factors with venous thromboembolism (VTE). Several genetic loci have been discovered and well-replicated for VTE in European descent populations. We examined associations of a genetic risk score (GRS), comprising known VTE loci, with chronic venous disease.<h4>Methods</h4>The San Diego Population Study (SDPS) is a multi-ethnic cohort that evaluated 2404 men and women aged 29-91 from 1994 to 1998 for chronic venous disease. ...[more]

PMID: 26442836

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Project description:BackgroundVenous thromboembolism (VTE) has been associated with a higher risk of developing malignancy and mortality, and patients with VTE may therefore benefit from increased surveillance. We aimed to construct a clinical predictive score that could classify patients with VTE according to their risk for developing these outcomes.MethodsObservational cohort study using an existing clinical registry in a tertiary academic teaching hospital in Buenos Aires, Argentina. 1264 adult patients greater than 17 years of age presented new VTE between June 2006 and December 2011 and were included in the registry. We excluded patients with previous or incident cancer, those who died during the first month, and those with less than one year of follow up (< 5%). 540 patients were included. Primary outcome was new cancer diagnosis during one year of follow-up, secondary composite outcome was any new cancer diagnosis or death. The score was developed using a multivariable logistic regression model to predict cancer or death.ResultsDuring follow-up, one-quarter (26.4%) of patients developed cancer (9.2%) or died (23.7%). Patients with the primary outcome had more comorbidities, were more likely to have previous thromboembolism and less likely to have recent surgery. The final score developed for predicting cancer alone included previous episode of VTE, recent surgery and comorbidity (Charlson comorbidity score), [AUC of 0.75 (95% CI 0.66-0.84) and 0.79 (95% CI 0.63-0.95) in the derivation and validation cohorts, respectively]. The version of this score developed to predict cancer or death included age, albumin level, comorbidity, previous episode of VTE, and recent surgery [AUC = 0.72 (95% CI 0.66-0.78) and 0.71 (95% CI 0.63-0.79) in the derivation and validation cohorts, respectively].ConclusionsA simple clinical predictive score accurately estimates patients' risk of developing cancer or death following newly diagnosed VTE. This tool could be used to help reassure low risk patients, or to identify high-risk patients that might benefit from closer surveillance and additional investigations.Trial registrationClinicalTrials.gov: NCT01372514.

Project description:Background Venous thromboembolism (VTE) is a threat to the prognosis of tumor patients, especially for critically ill patients. No uniform standard model of VTE risk for critically ill patients with tumors was formatted by now. We thus analyzed risk factors of VTE from the perspectives of patient, tumor, and treatment and assessed the predictive value of the ICU-VTE score, which consisted of six independent risk factors (central venous catheterization, 5 points; immobilization ≥ 4 days, 4 points; prior VTE, 4 points; mechanical ventilation, 2 points; lowest hemoglobin during hospitalization ≥ 90 g/L, 2 points; and baseline platelet count > 250,000/μL, 1 points). Methods We evaluated the data of tumor patients admitted to the intensive care unit of the Peking University Cancer Hospital between November 2011 and January 2022; 560 cases who received VTE-related screening during hospitalization were chosen for this retrospective study. Results The inhospital VTE occurrence rate in our cohort was 55.7% (312/560), with a median interval from ICU admission to VTE diagnosis of 8.0 days. After the multivariate logistic regression analysis, several factors were proved to be significantly associated with inhospital VTE: age ≥ 65 years, high tumor grade (G3–4), medical diseases, fresh frozen plasma transfusion, and anticoagulant prophylaxis. The medium-high risk group according to the ICU-VTE score was positively correlated with VTE when compared with the low-risk group (9–18 points vs. 0–8 points; OR, 3.13; 95% CI, 2.01–4.85, P < 0.001). The AUC of the ICU-VTE scores according to the ROC curve was 0.714 (95% CI, 0.67–0.75, P < 0.001). Conclusions The ICU-VTE score, as well as tumor grade, might assist in the assessment of inhospital VTE risk for critically ill patients with tumors. The predictive accuracy might be improved when combining two of them; further follow-up researches are needed to confirm it. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-022-02705-z.

Dataset Information

A genetic risk score comprising known venous thromboembolism loci is associated with chronic venous disease in a multi-ethnic cohort.

Publications

A genetic risk score comprising known venous thromboembolism loci is associated with chronic venous disease in a multi-ethnic cohort.

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